This document discusses the approach to diagnosing and treating myopathies. It begins by defining myopathies as disorders affecting skeletal muscle structure or function. Diagnosis involves clinical features and investigations such as elevated creatine kinase levels. Common presentations include proximal or distal muscle weakness. Electromyography and muscle biopsy are important for diagnosis. Myopathies can be classified as acquired, hereditary, or inflammatory. Inflammatory myopathies like polymyositis, dermatomyositis, and inclusion body myositis are described in detail. Treatment involves glucocorticoids and immunosuppressive drugs to improve muscle strength and control extramuscular symptoms. Prognosis depends on type of myopathy.

1. APPROACH TO
MYOPATHY
MODERATOR- DR.T.P.SINGH
DR.A.RAJ
PRESENTED BY-
KESHRI YADAV

2. Skeletal muscle diseases or myopathies,are
disorders with structural changes or functional
impairment of muscles.
Diagnosis of myopathy is based upon clinical
features of patients and investigations.

3. Muscle weakness – ADULTS
proximal muscle weakness - leading to complaints such
as difficulty arising from a chair or low toilet and
climbing stairs, a waddling gait or difficulty lifting
objects over the head, combing hair or brushing
teeth.eg. Muscular dystrophies, DM type 2,
metabolic, PM,DM
Distal muscle weakness - Presents with difficulty in
turning keys in holes,grasping things in hands,falls on
uneven ground.eg. Distal myopathies, dystrophica
myotonica type 1, dysferlin deficiency
Neck muscle weakness – inability to control neck while in
a vehicle as it rapidly accelerates and decelerates.
eg. occulopharyngeal dystrophy , inflammatory
myopathies

4. Cranial musculature - facial weakness (inability to
close eyes fully,difficulty in drinking with straw)
ptosis and extraoccular muscle involvement.
Diplopia is not common, unlike in NM junction
disorders and neural disorder. Eg. OP dystrophy,
DM1, FSHD
trunk muscles - leads to scoliosis, lumbar lordosis
and protuberant abdomen. eg. LGMD,
CHILDREN - hypotonia, delayed sitting,
standing,(Delayed milestones)

5. FATIGUE AND EXERCISE INTOLERANCE
 Fatigue - an inability to maintain or sustain a force.
Asthenia - fatigue caused by excess tiredness or lack of energy.
 Try to discriminate between physical and mental fatigue.
objective weakness
ABSENT - consider depression, anxiety neurosis.
PRESENT - consider it myopathy.eg. Metabolic,mitchondrial
Fatigue elicited after brief exericse – glycogenesis disorder
Fatigue elicited after long exericse – lipid metabolic disorder
MYALGIA MC Cause – orthopedic, rheumatic condition
Myopathies less frequent cause
 Constant proximal myalgia – PM, DM
 Episodic - metabolic

6. CRAMPS
 These are involuntary contractions of muscle that
usually last for several seconds to minutes.
 Most cramps are benign innature and occur
predominantly in calves. old age, dehydration, use
of diuretics,hypothyroid state, and a number of
other metabolic disturbances.
 In neuromuscular patients, they are most common
in motor neuron diseases, especially early
amyotrophic lateral sclerosis, and in chronic motor
or sensori-motor polyneuropathies.
 In myopathies, cramps are only common in
metabolic myopathies such as myophosphorylase
deficiency(McArdle’s disease), and in hypothyroid
myopathy.

7. CONTRACTURES
 Joint contractures are uncommon in patients
with muscular sympoms
 INITIAL PRESENTATION - most cases of
autosomal dominant or recessive and all cases
of X-linked recessive Emery-Dreifuss
myopathy, and in dystrophies caused by
mutations in collagen genes such as Bethlem
myopathy.
DURING ILLNESS PRESENTATION - Duchenne
and other muscular dystrophies and early in
juvenile dermatomyositis.

8. MYOTONIA
 Myotonia is characterized by impaired relaxation
after sustained voluntary contraction.
 This painless phenomenon commonly involves intrinsic
hand muscles and eyelids. It is due to tetanic
contraction of the fibers.
 Clinical assesment by –
tapping the muscle - percussion myotonia
voluntary contractions of muscle groups - action
myotonia.
 With repeated exercise
ALL MYOTONIA - Improves
PARAMYOTONIA – Worsens(paradoxical phenomenon)
 Cold exposure - makes both worse
 Causes - sodium or chloride channelopathies ,
myotonic dystrophies.

9. MYOGLBINURIA
presence of cola coloured urine.
Causes - unaccustomed strenuous exercise,
after drugs or toxin intake and infections, in
the wake of prolonged fever or heat stroke,
etc.
In case of recurrent myoglobinuria,
glycogenoses, lipid storage myopathies or
central core disease with malignant
hyperthermia have to be excluded.

10. Important History
family history
Drug history – ART,statins,steroids, diuretics
Personal history – alcohol intake,drug abuse,
heroin,cocaine,amphetamin
Sleep,appetite,weight gain,weight loss
Seizure, trauma
 bowel bladder involvement
Sensory symptoms eg. Tingling ,numbness
Asymmetrical weakness (except in IBM)

11.  In motor unit points in favour of myopathy :
 Muscle appearance – wasting ,atrophy
 ABSENT fasciculations
 Tenderness on palpation
 Tone –normal ,decreased in advanced cases.
 Distribution of weakness –proximal,distal (distal
myopathies)
 Tendon reflexes – normal /hypoactive
 Babinski sign -absent
 SENSORY system is normal.
 GAIT – lordosis on stance,increased on toe walking
 Waddling gait – b/l pelvic girdle weakness

12. Creatinine kinase single most useful initial laboratory
study in a suspected myopathy pt.
 CK is elevated in most patients with structural muscle disease.
 Normal CK in myopathies - mild or slowly progressive disease
1. in end stage myopathy with extreme muscle atrophy,
2. steroid-treated inflammatory myopathies and rare cases of
untreated dermatomyositis
3. atypical inflammatory myopathies associated with a collagen
vascular disease
4. Alcohol/steroid-related or endocrine myopathies (except
hypothyroid)
 CKMM elevation is typical of myopathies, but CKMB is also
increased in most of these subjects and can not be used as evidence
of an associated cardiomyopathy.
 Consider myopathy if CK is elevated more than 3 times normal value
with myalgia, muscle weakness,
 Other causes of CK elevation - muscle trauma (after EMG study,
injections), viral infections,seizures or strenuous exercise may all be
accompanied by transient but severe CK elevation.
Drugs - lipid lowering drugs, chloroquine, cyclosporine A,AZT, etc.

13. Electromyography
 Use of EMG –
(1)To confirm a suspected myopathy and to exclude other
disorders that may mimic myopathy.
(2)May provide clues to the etiology of a suspected
myopathy.
(3) Assists in the selection of the biopsy site or in
assessment of the treatment response.
 Normal EMG found in - corticosteroid
myopathy, many congenital myopathies and some
metabolic and endocrine myopathies .
Repetitive Nerve stimulation(RNS)
Nerve conduction studies
 Normal in myopathy.Used to exclude NM diseases.
 Low compound muscle action potential (CMAP)amplitudes
may occur in a number of distal myopathies.
 More than 50% direct loss of muscle fibers is needed to
significantly reduce the CMAP amplitude.

14. NEEDLE EMG
 Reveal irritability on needle placement s/o,dystrophies,toxic
inflammatory,myotonic myopathies,
 The combined findings in the muscle at rest, i.e. Spontaneous
activity and abnormal insertion activity, and during voluntary
contraction, i.e. early recruitment of small, short duration low
amplitude motor unit potentials (MUPs), reflect the underlying
pathology affecting the muscle fibers.
 Abnormal insertional activity-Complex repetitive discharges
(CRD) Myotonic discharges
 CRD - vacuolar myopathies, e.g. acid maltase deficiency and in
the inflammatory myopathies
 Myotonic discharges are repetitively occurring single fiber
action potentials that are waxing and waning in amplitude and
firing rate, producing the characteristic
“dive bomber” sound.
 They are quite specific for the myotonic dystrophies and
disorders of sodium or chloride channel dysfunction.

16. CLASSIFICATION
Acquired myopathies
 Inflammatory myopathies
 Endocrine myopathies
 Toxic or drug-induced myopathies
Hereditary myopathies
 Muscular dystrophies
 Congenital myopathies
 Myotonias and channelopathies
 Metabolic myopathies
 Mitochondrial myopathies

17.  Largest group of acquired and potentially treatable
causes of skeletal muscle weakness .
 POLYMYOSITIS (PM)
 DERMATOMYOSITIS (DM)
 INCLUSION BODY MYOSITIS (IBM)
 1 :1,00,000
 PM – as alone is a rare disease affecting ADULTS.
 DM – affects both children,adults W>M
 IBM – M:F –3:1 ,caucasians,>50yrs.

18.  Autoimmune etiology - assosciation with other autoimmune
CTD ,various Auto Ab, MHC ,T CELL myotoxicity,complement,
response to immunotherapy.
 AUTOANTIBODIES AND IMMUNOGENETICS:
 20% cases – ANA,anti cytoplasmic antigens
 Anticytoplasmic – anti RNP(anti synthetase),
 Anti jo 1 – 75% cases -80% assosciation with ILD.
 Anti Jo 1 –ILD ,RP,non erosive arthritis,MHCDR3,DRw52.
 DRB1 *0301,DQB1*0201 --- 75% PM,IBM
 DQA1*0501 –juvenile DM

19.  Coxsackie,influenza,paramyxoviruses,mumps,CMV,EBV.
 Autoimmune myositis in coxsackie virus
 Molecular mimicry of Anti RNAsynthetase and genomic
RNA .
 Best evidence of viral connection in PM,IBM –retroviruses.
HIV,HTLV 1 – PM,IBM
 May be the initial manifestation or later of viral infection.
 Retroviral antigens –endomyosial macrophages ,but not in
muscle fibres.
 AZT induced myopathy –mitochondrial – ragged red fibres.
 AZT inhibits gamma DNA polymerase.

20. In general :
 PROGRESSIVE AND SYMMETRIC MUSCLE weakness (IBM –
asymmetric).
 Increasing difficulty with tasks – getting up from
chair,climbing steps,lifting objects,combing hair.
 Occular muscles are spared –even in advanced ,untreated
cases –if involved ? Diagnosis
 Head drop sign - weakness of neck flexors
 dysphagia – weakness of esophageal muscles
 Respiratory muscles involved in advanced cases.
 Muscle wasting in untreated cases .
 Sensation always normal .
 DTR preserved.

21.  Subacute inflammatory myopathy affecting adults,rarely
children.
 Diagnosis by exclusion.
 As an isolated entity it is rare.
 Commonly occurs in assosc.
With systemic autoimmune
disease ,viral,bacterial infection.
 Drugs –AZT,D penicillamine, lipid
lowering drugs
Who DONOT Have
1.Rash
2. EOM,facial muscles
3.Family H/O NMD
4.h/o myotoxic drugs,toxins
5.endocrinopathy
6.Neurogenic disease
7.Muscular dystrophy
8.Bicohemical disorder
9.IBM

22. Characteristic rash accompanying/preceding muscle weakness
 heliotrope rash - Blue purple discoloration on the upper
eyelids with edema.
 gottron’s sign - Erythema of the knuckles with a raised
violaceous scaly eruption.
 V sign Erythematous rash on anterior chest –.
 shawl sign - Back and shoulders .
 Mechanic’s hands –irregular dirty horizontal lnies on the
palmar surface of fingers.
 Dermatomyositis sine myositis – muscle strength normal
 Photosensitivity present.
 Erythemaous rash on face and upper chest.
 Dilated capillary loops at the base of the finger nails.
 Muscle tenderness,myalgia –connective tissue disease.
 Perivascular perimysial inflammation

24.  >50 yrs of age,
 most common inflammatory myopathy.
 Often misdiagnosed as PM
 Suspected when does not respond to therapy.
 Weakness and atrophy of distal muscles,foot extensors,deep
finger flexors –all cases –clue to early diagnosis.
 mild facial muscle weakness is common in patientswith IBM.
 Fine motor movements –affected early
 Falling is common – quadriceps –buckling of knees.
 DTR –depressed in presence of atrophy .
 Dysphagia -60% cases
 Slow and steady progression (over years)
 Assisted devices required

25.  20 % CASES -systemic autoimmune or connective tissue
disease.
 Familial IBM
 Hereditary IBM - heterogenous group of recessive,dominant
inherited syndromes,non inflammatory
 May spare the quadriceps –iranian JEWS
 Chromosome 9p1
 Mutations in the UDP – N acetylglucosamine 2- epimerase n –
acetylmannosamine kinase GNE gene.

28. EXTRAMUSCULAR MANIFESTATIONS:
 Systemic symptoms --- fever,malaise -- CTD.
 Joint contractures –DM in children
 Dysphagia ,GI abn – DM ,IBM
 Cardiac disturbances –arryhthmias,DCMP,CCF
 Pulmonary dysfunction – ILD,drug induced – t RNA ab – 10%
 Subcutaneous calcifications –DM
 Arthralgias,deforming arthropathy – anti jo1 ab
MALIGNANCIES – DM(dermomyositis) Nasopharyngeal in india
 Ovarian,breast,melanoma ,colon,NHL
OVERLAP SYNDROMES – DM – SSc,PM – RA ,sjogren’s,SLE
 Anti PM/Scl - overlap syndrome of DM.

29.  GOAL : improve muscle strength,ameliorate
extramuscular manifestations.
 Discontinue the drugs if after trial no improvement
of muscle strength.
 1.GLUCOCORTICOIDS :oral prednisolone –high doses –
1mg/kg/day – 3-4 weeks,taper later 10 weeks –
1mg/kg every other day.
 Lowest possible dose to be used.
 Efficacy by third month
 PM > DM better in response.
 Steroid myopathy – increased weakness –2- 8 weeks.

30.  2.IMMUNOSUPPRESSIVE THERAPY :
 75% patients ultimately require.
 A.AZATHIOPRINE : 3mg/kg/day
 B.MTX : 7.5 mg weekly for the first 3 weeks then add-
2.5mg/wk-max. 25 mg/wk --- MTX pneumonitis.
 C.mycophenolate MOFETIL – 2.5 mg/d
 D.rituximab - IN DM
 E.CYCLOSPORINE – inconsistent benefit
 F.TACROLIMUS - PM difficult cases.
 3.IMMUNOMODULATION:
 IVIg in refractory DM -short term benefit
 2g/kg over 2-5 days /course.
 PLASMAPHERESIS,LEUKOPHERESIS - NOT EFFECTIVE IN
PM,DM

31.  IBM or metabolic myopathy,muscular dystrophy,
endocrinopathy.
 Repeat muscle biopsy
 Calcinosis of DM –difficult to treat
 IBM –resistant to immunosupressive therapy
 Drugs not to be withdrawn(subjective weakness)
 IVIg and prednisolone – not effective
 PROGNOSIS -5 yr surivival – 95%,10 yr -85%
 Best prognosis – DM, worst prognosis - IBM
 Death –pulmonary,cardiac
 Worse prognosis – older,severe mainfestations at
prsentation

32. Causes
1. Thyroid disorders ( hypo, hyper)
2. Adrenal disorders ( cusshing syn. Conn’s syndrome)
3. Parathyroid disorders ( hypo, hyper)
4. Pitutary disorder ( acromegaly)
5. Diabetes mallitus
6. Vitamin D deficiency
Cardinal features
 Muscle fatigue is more common than true weakness.
 Serum CK,EMG and muscle histology Normal.
except – hypothyroidism (CK elevated)
 All respond to treatment

33. THYROID DISORDERS:
HYPOTHYROIDISM
 proximal muscle weakness-1/3
 Slow muscle contraction and relaxation
-25% cases.
 Relaxation phase prolonged –
ankle,biceps reflex-hung up reflex
 RX – thyroxin 1.6 ug/kg
HYPERTHYROIDISM:
 Proximal muscle weakness,atrophy of
muscles.
 DTRs enhanced response.
 Bulbar,esophageal,respiratory muscles
affected.
 Fasciculations+DTRs –ALS misdiagnosis
 Acquired hypokalemic periodic
paralysis,MG,graves ophthalmopathy
THYROID MYOPATHY
1.CHRONIC
THYROTOXIC
MYOPATHY
2.GRAVES
OPHTHALMOPATHY
3.THYROTOXIC
HYPOKALEMIC
PERIODIC PARALYSIS
4.MYASTHENIA GRAVIS
ASS WITH HYT.
5.HYPOTHYROID
MYOPATHY

34. Adrenal Disorders
 Steroid myopathy - Most commonly diagnosed
endocrine muscle disease.
 Proximal muscle weakness present.
 Muscle wasting accompanies cushingoid
appearance.
 Type 2b fibres atrophy on histology, so EMG is
Normal.
 Primary hyperaldosteronism(CONN’S syndrome )-
proximal muscle weakness.
 Muscle weakness due to K+ depletion not due to
direct effect of aldosterone on muscles.
 Serum CK LEVELS ELEVATED,vacuoles on biopsy.

35.  LIPID LOWERING AGENTS – fibrates ,statins& niacin
 GLUCOCORTICOIDS – acute quadriplegic paralysis(high dose iv
steroid) chronic proximal myopathy(>30mg/d prednisone use)
 Mainly flourinated-dexa,beta,triacinolone.
 ART – Zidovudine 17% (mitochondrial myopathy with ragged
red fibres) >1200mg/day for 6months. with no inflamation
 DRUGS OF ABUSE AND RELATED MYOPATHY-
Alcohol,Amphetamines,Cocaine,Heroin, Phencyclidine, Meperidine
(rhabdomyolysis , myoglobinuria)
 NON DEPOLARIZING NM BLOCKING AGENTS (acute quadriplegic
paralysis)
 DRUG INDUCED AUTOIMMUNE MYOPATHIES – D penicillamine
(polymyositis, myasthenia gravis)
OTHERS - amiodarone, chloroquine, hydroxychloroquine,
colchicine(proximal muscle weakness)

36.  Acute quadriplegic myopathy/acute steroid myopathy
 In cases of severe asthma ,sepsis and shock.
 Neuromuscular blocking agents in 80% cases.
 High doses of corticosteroids 1mg/kg ,pancuronium -500-
4,000 mg
 Difficulty in weaning from the ventilator
 Tendon relfexes are normal- diminished –polyneuropathy
 Serum CK levels elevated.
 EMG –MYOPATHY with type 2 fibers vacuolation.
 Striking loss of myosin filaments
 Severe cases– myoglobinuria,renal failure.
 Denervation of muscles –increase in glucocorticoid receptors
 Recovery over 6- 12 weeks
Neuromus
cular
blocking
agents
Muscle
denervation -
Increase in the
glucocorticoid
receptors
Myosin
filaments
loss

37. X linked muscular
dystrophies
Duchenne muscular dystrophy
Becker muscular dystrophy
Emery-driefuss muscular dystrophy
Scapuloperoneal
Autosomal dominant Facioscapulohumoral muscular
dystrophy
Occulopharyngeal muscular dystrophy
Limb girdle muscular dystrophy (1A-
1E)
Emery-driefuss muscular dystrophy
Autsomal recessive Limb girdle muscular dystrophy(2A-
2M)
Congenital muscular dystrophy

38. Group of inherited myopathies characterised
by progressive muscle weakness and wasting.
Subdivided on the basis of mode of
inheritence,age at onset,distribution ,rate of
progression and prognosis.

39. MC muscular dystrophy.
Gene mutation - dystrophin. X recessive
Incidence – 30/100000 births
Calf and deltoid hypertrophy
Gower’s maneuver on rising from floor.
Mental retardation.
Duchenne's dystrophy is present → at birth
but becomes apparent → b/w 3 and 5 years.

40.  by age 6 years → toe walking with a lordotic
posture.
Contractures of the achillis and iliotibial bands.
 Between ages 8 and 10 years → walking may
require the use of braces; joint contractures and
limitation of movments.
 By age 12 years, → most patients are wheelchair
dependent.
 By age 16–18 years → patients are predisposed
to serious, sometimes fatal pulmonary infections.
Other causes of death include aspiration of food
and acute gastric dilation.
 By age 20 years → patient dies.

41. Difficulty rising
(Gower’s sign)

42.  In the early stages,
Duchenne MD affect
the pectoral muscles ,
the trunk, hamstrings,
calf muscle.
 Mental retardation
also common.

43. PSEUDOHYPERTROPHY
ATROPHY

44.  Muscle enzymes
Creatinine kinase [CK]-20-100 times of Normal.
 Muscle biopsy-investigation of choice.
 Electromyogram-features of myopathy.
 Treatment –
Glucocorticoids, administered as prednisone in a dose
of 0.75 mg/kg per day, significantly slow progression
of Duchenne's dystrophy for up to 3 years.

45.  an incidence of about 3 per 100,000 live-born males.
 Less severe than DMD.
 Onset between 5 and 15 yrs.
 Ambulatory beyond age 15 yrs while in DMD typically on
wheelchair at 5 yrs.
 CMP may occure with CHF BUT mental impairment
uncommon.
 CPK,EMG,and muscle biopsy closly resemble to DMD.
 Pateint doesn’t respond to steroid therapy.

46. Two types on the basis of overlapping
phenotypes and distinct molecular genetic
defects:
myotonic dystrophy type 1 (DM1) -
chromosome 19q,expansion of CTG repeats
myotonic dystrophy type 2 (DM2/PROMM)
chromosme 3q, expansion of CCTG repeats

47. Clinical features of DM1
Myotonia apears by 5 years.
hatchet-faced appearance- temporalis, masseter,
and facial muscle atrophy.
Distal weakness - Weakness of wrist
extensors,finger extensors, and intrinsic hand
muscles impairs function. Ankle dorsiflexor
weakness may cause footdrop.
Other features - Frontal baldness,cataracts,mental
impairment CHB, MVP,Insulin resistance and
gonadal atrophy are common.

48. Clinical features of DM2
It has a distinct pattern of muscle weakness
affecting mainly proximal muscles.
Cardiac conduction defects occur but are less
common, and the hatchet face and frontal
baldness are less consistent features.

49. Investigations
 CK – normal to elevated
 EMG – myotonia present . It sounds similar to reviving of
motorcycle.
 Muscle biopsy - shows muscle atrophy, which selectively
involves type 1 fibers in 50% of cases, and ringed fibers in
DM1 but not in DM2.
Treatment
 The myotonia in DM1 rarely warrants treatment.
 Though some patients with DM2 are significantly bothered
by the discomfort related to the associated muscle stiffness.
 Phenytoin and mexiletine are the preferred agents.
other agents, particularly quinine and procainamide, may
worsen cardiac conduction.

50. FSHD1 is associated with deletions at 4q35
FSHD2-no deletion of 4q both have
hypomethylation leading to toxic
menifestation of DUX4 gene,
initial manifestation → facial weakness
Weakness of the shoulder girdles, rather than
the facial muscles, usually brings the patient
to medical attention.

51. Facial weakness →biceps,triceps,shoulder girdle
(winging of scapula)→wrist extensor →anterior
compartment of leg.
No Cardiac involvement,deltoid is spared.
CPK may be Normal/mildly elevated.
No specific treatment required.foot arthoses and
scapular stablization procedures are helpful

52.  Late onset (4th to 6th decade),expansion,polyA RNA
binding protein.
 Ptosis and dyphagia are common presentation.
 progressive external ophthalmoplegia
ptosis + limitation of eye movements
sparing of pupillary reactions
 Muscle biopsy - muscle fibers are found to contain
rimmed vacuoles.
Treatment -
 Cricopharyngeal myotomy may improve swallowing,
although it does not prevent aspiration.
 Eyelid crutches can improve vision when ptosis
obstructs vision

53. AR/AD,affect pelvic and shoulder girdle
muscles,no mental impairment
Defect of sarcoglycon
Respiratory insufficiency,cardiac involvement-
CHF/arrythmias; ocasionaly CMP
AD-LGMD1A-1E
AR-LGMD2A-2O except LGMD2E

54.  This is achieved by studying the foetus’s own DNA on
a chorion villus biopsy.
 The test is performed on a tiny piece of the
developing placenta usually at the 11th –12th week of
pregnancy.

55. Classification
1. Merosin deficiency (merosin)gene-laminin alfa2 chain
2. Fukitin-related protein deficiency (fukitin)
3. Fukuyama congenital muscular dystrophy (fukitin)
4. Muscle-eye-brain disease
(N-acetyl-glucosaminyl transferase/POMGnT1)
5. Walker-Warburg syndrome
(O-mannoxyl-transferase-1/POMT1)
 Three forms of congenital muscular dystrophy
have severe brain impairment- FCMD, MEB
disease, WWS.
 Worst prognosis – Walker warburg syndrome

56. Common clinical features
1. Onset at birth, hypotonia
2. Generalized muscle weakness
3. Joint contractures(arthrogryposis)
Treatment
There is no specific treatment for CMD.
Proper wheelchair seating is important.
Management of epilepsy and cardiac
manifestations is necessary for some patients.

57. Rare and relatively nonprogressive disorder
Begins in infancy/childhood but apparent in
adulthood
Proximal weakness,hypotonia,hyporeflexia
and normal CPK.
differenciated from dystrophies by specific
structural and histochemical abnormality.

58. AD,biopsy shows fibers with single/multiple
central/ecccentric discrete zones (core)devoid
of oxydative enzymes (esp.in type1 fibers)
C/F-have decreased fetal movement and
breech presentation,delay in moter
milestones(perticularly walking).

59. Muscle biopsy shows clusters of small
rods(nemalin bodies-thread like
structures),but not exclusive for type 1 fibers.
Clinically hetrogenous. Facial and generalized
muscle weakness is common.

60. Muscle biopsy shows-rows of central nuclei
often surrounded by a halo.
Three distinct variants are known to occur-
Neonatal form
Late infancy early childhood
Late childhood.

61. Late onset,>40 yrs
Dominantly
inherited
WELANDER
Markesbery -
Griggs
Udd ,tibial
muscular
dystrophy
WELANDER
MYOPATHY
WRIST ,FINGER
EXTENSORS
MARKESBERY,UDD
ANTERIORTIBIAL
WEAKNESS
FOOT DROP
• DOMINANT,TIBIAL WEAKNESS
• CHILDHOOD IN ONSET
• RIMMED VACUOLES ON BIOPSY
LAING DISTAL
MYOPATHY
• AR inheritance.
• NONAKA - -- ANTERIOR TIBIAL WEAKNESS
• MIYOSHI – GASTROCNEMIUS.,ELEV.CK,ABSENT
DYSFERLIN
NONAKA
DISTAL,MIYOSHI
MYOPATHY
• AD/AR,CLINCALLY HETEROGENOUS
• MYOTONIC DISCHARGES ON EMG
• DENSE INCLUSION ON BIOPSY,DESMIN
MYOFIBRILLAR
MYOPATHY

62. •ADOLESCENCE,M>W,HIGH CARB DIET,REST AFTER EXERCISE,CARDIAC
ARRYHTHMIAS
•TYPE 1 –AD,CALCIA3 GENE,10% TYPE 2 –SCN4
•RX—ORAL KCL -0.2-0.4MMOL/Kg EVERY 30 MIN(,MANNITOL-
vehicle),oral acetazolamide 500 bd reduces attacks in type1
•LOW CARB,LOW SODIUM DIET,ACETAZOLAMIDE MAY ABOLISH
ATTACKS(exacerbated IN TYPE2)
• thyrotoxic PP resembles but w>M AGE >25
CALCIUM CHANNEL
–HYPOKALEMIC
PERIODIC PARALYSIS
•MISNOMER – AD IN INHERITANCE
•PROXIMAL MUSCLES ,BULBAR ARE SPARED.
•MYOTONIA WITHOUT WEAKNESS –COLD STIFFNESS
•LESS VACUOLES,MORE PERIPHERAL
•ACETAZOLAMIDE,MEXILITINE
SODIUM CHANNEL
–HYPERKALEMIC
PERIODIC PARALYSIS
•MYOTONIA WORSENS WITH MUSCULAR ACTIVITY
•SENSORY,MOTOR NERVE CONDUCTION STUDIES ARE NORMAL
•MYOTONIC DISCHARGES DISAPPEAR ON COOLING
•AD,SODIUM CHANNEL
•INCREASED CARBOHYDRATE IN THE DIET,MEXILITENE,THIAZIDE
DIURETICS
SODIUM CHANNEL
PARAMYOTONIA
CONGENITA

63.  POTASSIUM CHANNEL DISORDERS:
 1.ANDERSEN TAWIL SYNDROME:
 Episodic weakness,dysmorphic features.
 cardiac arrythmias are life threatening.
 autosomal dominant
 kir 2.1 gene
 Acetazolamide
 CHLORIDE CHANNEL DISORDERS:
 AD –THOMSEN’S DISEASE
 AR – BEKER’S DISEASE
 Myotonia worsened by cold,improved by activity
 Muscle strength normal in thomson’s
 Quinine,mexiletine,phenytoin.

64. Ppted by brief
bursts of high
intensity
exercise
Warm up exercise
helpful in mc ardles’s
disease
Hemolytic anemia
seen with
phosphofructokinase
deficiency
Phosphoglycera
te kniase –
mental
retardation,Fore
arm exercise
test
• Infantile form most common
• Glycogen accumulation occurs in neurons
• Childhood form –muscular dystrophy,only heart
• Heart and liver not involved in adult ,resp
.failure
Acid maltase deficiency
(pompe’s disease) (AR)
• Slowly progressive
• Diagnosed in infancy with
hypotonia,hepatomegaly
• hypoglycemia
Debranching enzyme
deficiency
Type III glycogenosis
•Rare AND FATAL
•HEPATOMEGALY
•SKELETAL MUSCLE MANIFESTATIONS ARE MINOR
Branching enzyme
deficiency
Type IV glycogenosis
MYOPHOSPHORYLASE
DEFICIENCY(TYPE V)
PHOSPHOFRUCTOKINASE (TYPE
VII)XLR
BETA ENOLASE DEFICIENCY

65. Carnitine
Palmiotyl transferase deficiency
Mc cause of recurrent
myoglobinuria
Muscle pain only after the limit
exceeded.
A normal rise in venous lactate on forearm
exercise test
CPT II deficiency more common in men than women
High carb diet
Myodenylate deaminase
deficiency
5 AMP –IMP +NH3
NO SYMPTOMS

66.  TERM RAGGED RED FIBRES –ABNORMAL MITOCHONDRIA ON MODIFIED
TRICHROME STAIN .
 Mitochondria are enlarged,bizarrely shaped,crystalline inclusions
 Most common is CPEO >50% cases of mitochondrial myopathies.
KEARNS SAYRE SYNDROME
ONSET<20 YRS,CPEO,PIGMENTARY
RETINOPATHY PLUS CHB,CSF
PROTEIN >1 G/L,CERBELLAR ATAXIA
DEATH DUE TO HEART BLOCK -20%
ENDOCRINE ABN ARE COMMON –
DIABETES MELLITUS -13%
MENTAL RETARDATION ,DEMENTIA
SERUM CK LEVLES NORMAL,SERUM
LACTATE AND PYRUVATE LEVELS
ELEVATED
MYOCLONIC EPILEPSY WITH
RAGGED RED FIBRES
MYOCLONIC EPILEPSY,CEREBELLAR
ATAXIA,PROGRESSIVE MUSCLE WEAKNESS
EPILEPSY –PRESENTING,LIMB GIRDLE
INVOLVEMENT
SERUM CPK NORMAL,SERUM LACTATE
ELEVATED
TYPICAL RAGGED RED
FIBRES ON MUSCLE BIOPSY
MELAS
MOST COMMON
MITOCHONDRIAL
ENCEPHALOMYOPATHY
NO STRICT VASCULAR
DISTRIBUTION-STROKE
LIKE
STROKE <40 YRS AGE
DEMENTIA,BEDRIDDEN,
FATAL STATE
SERUM LACTIC ACID
ELEVATED
T RNA MUTATIONS -
LETHAL